Non-inflammatory cerebrospinal fluid delays the diagnosis and start of immunotherapy in anti-NMDAR encephalitis

ABSTRACT

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalopathy that presents with a wide variety of symptoms, including neuropsychiatric manifestations. The authors’ aim for this study was to analyze the results of paraclinical studies of patients with a diagnosis of anti-NMDAR encephalitis and the association between symptom onset and diagnosis, and start of immunotherapy. Retrospective data of 29 patients with anti-NMDAR encephalitis were gathered and analyzed. Abnormal EEG was found in 27 patients (93.1%), whereas MRI was abnormal in 19 patients (65.5%). In contrast, an inflammatory pattern on CSF analysis was found in only 13 patients (44.8%). The absence of pleocytosis or increased proteins in the CSF was associated with a longer time from symptom onset to diagnosis and treatment (p = 0.003). The authors conclude that noninflammatory CSF may delay the correct diagnosis and start of immunotherapy in anti-NMDAR encephalitis. In the presence of suggestive clinical features, extensive studies including EEG are recommended.

RESUMEN

La encefalitis por receptor anti-N-metil-D-aspartato (anti-NMDAR) es una encefalopatía autoinmune con una amplia variedad de síntomas, incluyendo manifestaciones neuropsiquiátricas. Nuestro objetivo en este estudio fue analizar los resultados paraclínicos de pacientes diagnosticados con encefalitis anti-NMDAR y la asociación entre inicio de sintomatología, el diagnóstico y el inicio de inmunoterapia. Encontramos un EEG anormal en 27 pacientes (93.1%), así como IRM anormal en 19 de ellos (65.5%). En contraste, el análisis de LCR mostró un patrón inflamatorio en tan solo 13 pacientes (44.8%). La ausencia de pleocitosis o proteínas incrementadas en el LCR se asoció con un mayor tiempo desde el inicio de la sintomatología hasta el inicio del tratamiento (p=0.003). Concluimos que el LCR no inflamatorio puede retrasar el diagnóstico correcto y el inicio de tratamiento en encefalitis anti-NMDAR, por lo que se recomienda la realización de estudios exhaustivos, incluyendo EEG, ante la presencia de indicadores clínicos sugerentes del padecimiento.

anti-n-methyl-d-aspartate receptor encephalitis - cerebrospinal fluid - diagnosis

encefalitis antirreceptor n-metil-d-aspartato - líquido cefalorraquídeo - diagnóstico

• References

• 1 Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A et al. Case definition, diagnosis algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013;57(8):1114-28. https://doi.org/10.1093/cid/cit458
• 2 Leypoldt F, Armangue T, Dalmau J. Autoimmune encephalopathies. Ann N Y Acad Sci. 2015;1338(1):94-114. https://doi.org/10.1111/nyas.12553
• 3 Lejuste F, Thomas L, Picard G, Desestret V, Ducray F, Rogemond V et al. Neuroleptic intolerance in patients with anti-NMDAR encephalitis. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e280. https://doi.org/10.1212/NXI.20170179201701790280
• 4 Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iisuka T et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013;12(2):157-65. https://doi.org/10.1016/S1474-4422(12)70310-1
• 5 Wang W, Li JM, Hu FY, Wang R, Hong Z, He L et al. Anti-NMDA receptor encephalitis: clinical characteristics, predictors of outcome and the knowledge gap in southwest China. Eur J Neurol. 2016;23(3):621-9. https://doi.org/10.1111/ene.12911
• 6 Byrne S, Walsh C, Hacohen Y, Muscal E, Jankovic J, Stocco A et al. Earlier treatment of NMDAR antibody encephalitis in children results in a better outcome. Neurol Neuroimmunol Neuroinflamm. 2015;2(4):e130. https://doi.org/10.1212/NXI.20170179201701790130
• 7 Sartori S, Nosadini M, Cesaroni E, Falsaperla R, Capovilla G, Beccaria F et al. Paediatric anti-N-methyl-D-aspartate receptor encephalitis: the first Italian multicenter case series. Eur J Paediatr Neurol. 2015;19(4):453-63. https://doi.org/10.1016/j.ejpn.2015.02.006
• 8 Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404. https://doi.org/10.1016/S1474-4422(15)00401-9
• 9 Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091-8. https://doi.org/10.1016/S1474-4422(08)70224-2
• 10 Florance NR, Davis RL, Lam C, Szperka C, Zhou L, Ahmad S et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol. 2009;66(1):11-8. https://doi.org/10.1002/ana.21756
• 11 Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS et al. N-methyl-D-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain. 2010;133(Pt 6):1655-67. https://doi.org/10.1093/brain/awq113
• 12 Viaccoz A, Desestret V, Ducray F, Picard G, Cavillon G, Rogemond V et al. Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis. Neurology. 2014;82(7):556-63. https://doi.org/10.1212/WNL.20170179201701790126
• 13 Zekeridou A, Karantoni E, Viaccoz A, Ducray F, Gitiaux C, Villega F et al. Treatment and outcome of children and adolescents with N-methyl-D-aspartate receptor encephalitis. J Neurol. 2015;262(8):1859-66. https://doi.org/10.1007/s00415-015-7781-9
• 14 Wright S, Hacohen Y, Jacobson L, Agrawal S, Gupta R, Philip S et al. N-methyl-D-aspartate receptor antibody-mediated neurological disease: results of a UK-based surveillance study in children Arch Dis Child. 2015;100(6):521-6. https://doi.org/10.1136/archdischild-2014-306795
• 15 Nagappa M, Bindu PS, Mahadevan A, Sinha S, Mathuranath PS, Taly AB. Clinical features, therapeutic response, and follow-up in pediatric anti-n-methyl-D-aspartate receptor encephalitis: experience from a tertiary care university hospital in India. Neuropediatrics. 2016;47(1):24-32. https://doi.org/10.1055/s-0035-1569464
• 16 Zhang L, Wu MQ, Hao ZL, Chiang SM, Shuang K, Lin MT et al. Clinical characteristics, treatments, and outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis: A systematic review of reported cases. Epilepsy Behav. 2017;68:57-65. https://doi.org/10.1016/j.yebeh.2016.12.019